Much research has attested to impairments associated with attention and concentration in children with sickle cell disease. However, few methods of remediation for these cognitive sequelae have been tested empirically. Due to the dearth of clinical trials specifically examining the safety and efficacy of pharmacotherapy for the remediation of cognitive sequelae associated with neurological complications in pediatric sickle cell disease, we propose two pilot studies designed to evaluate the efficacy and safety of methylphenidate (MPH), a widely used stimulant medication. Thus, a general hypothesis of this pilot research program is that MPH is effective in reducing cognitive impairments associated with neurological complications among children with the HbSS genotype of sickle cell disease. Specifically, in a randomized, double-blind, placebo-controlled, cross-over trial, we plan to establish the acute efficacy of MPH on laboratory-based measures of sustained attention, reaction time, executive functions, and verbal short-term memory in children with sickle cell disease. In the second pilot study, we plan to evaluate the ecological validity of MPH in pediatric sickle cell disease, by conducting a randomized, double-blind, placebo-controlled, cross-over trial, to establish the short-term efficacy of MPH in enhancing attention at home as rated by caregivers, attention in the classroom as rated by teachers, behaviors associated with executive dysfunction as rated by caregivers and teachers, and social skills as rated by caregivers and teachers. In addition, an evaluation of safety and cognitive toxicity of MPH will be conducted. Thus, the proposed study represents a first stage of research in the psychopharmacology of cognitive impairments and learning problems among children with sickle cell disease. As a follow-up to the proposed pilot study, we plan to examine by means of a long-term clinical trial, the enduring effectiveness and safety of stimulant medication in the management of attentional problems in children and adolescents with sickle cell disease. [unreadable] [unreadable]